: The project will study myelin/ oligodendrocyte glycoprotein (MOG) which has been localized on the outermost wrap of the myelin sheath and identified as a major target involved in immune-mediated demyelination. The proposal has three Specific Aims that are overall designed 1) to advance the understanding of MOG and the role it plays in myelination and 2) to begin a molecular analysis of MOG's interactions with the oligodendroglial cytoskeleton. Since preliminary data indicate that MOG interacts with the cytoskeleton, the project will focus on MOG's putative cytoplasmic domains that are most likely to associate with the cytoskeleton. In Aim 1, MOG's cytoplasmic domains will be mutagenized to generate constructs which in turn will be used to generate multiple stable transfectants of an immortalized oligodendrocyte cell line N20.1. In Aim 2, MOG/cytoskeleton interactions will be analyzed in wildtype and variant MOG stably expressing N20.1 lines. In Aim 3, the proposal will focus on characterizing molecules that associate with MOG's intracellular domains, utilizing co-immuno-precipitation and cross-linking experiments.